Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).

This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS).

Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; P = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; P = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; P = .02), 76.2% (HR, 1.02; 0.60 to 1.72; P = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; P = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; P = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; P = .037).

CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.

钙调神经磷酸酶抑制剂 (CNI) 是造血细胞移植 (HCT) 后移植物抗宿主病 (GVHD) 预防的标准成分。先前的数据表明，使用供体 T 细胞耗竭的无 CNI 方法，无论是通过离体 CD34 选择还是体内移植后环磷酰胺 (PTCy) 作为单一药物，与较低的慢性 GVHD (cGVHD) 发生率相关。

这项多中心 III 期试验随机分配患有急性白血病或骨髓增生异常的患者和 HLA 匹配的供体，接受 CD34 选择的外周血干细胞、骨髓 (BM) 移植后接受 PTCy，或 BM 移植后接受他克莫司和甲氨蝶呤（对照）。主要终点是cGVHD（中度或重度）或无复发生存期（CRFS）。

在 346 名入组患者中，327 名患者接受了 HCT，每个方案 300 名患者接受了 HCT。 CD34 选择的 2 年 CRFS 意向治疗率为 50.6%（与对照相比，风险比 [HR] 为 0.80；95% CI，0.56 至 1.15； P = .24），PTCy 为 48.1%（HR， 0.86；0.61 至 1.23； P = .41)，对照为 41.0%。相应的总生存率为 60.1%（HR，1.74；1.09 至 2.80； P = .02）、76.2%（HR，1.02；0.60 至 1.72； P = .95）和 76.1%。 CD34 选择与较低的中度至重度 cGVHD 相关（HR，0.25；0.12 至 0.52； P = .02），但与较高的移植相关死亡率相关（HR，2.76；1.26 至 6.06； P = .01）。 PTCy 与可比的 cGVHD 和对照生存结果相关，并且具有较低疾病复发的趋势（HR，0.52；0.28 至 0.96； P = .037）。

与他克莫司和甲氨蝶呤联合 BM 相比，本文中进行的无 CNI 干预并未产生更好的 CRFS。较低的中度和重度 cGVHD 发生率并没有转化为生存率的提高。